Background

Several environmental contaminants were shown to possibly influence fetal growth, generally from single exposure family studies, which are prone to publication bias and confounding by co-exposures. The exposome paradigm offers perspectives to avoid selective reporting of findings and to control for confounding by co-exposures. We aimed to characterize associations of fetal growth with the pregnancy chemical and external exposomes.

Methods

Within the Human Early-Life Exposome project, 131 prenatal exposures were assessed using biomarkers and environmental models in 1287 mother–child pairs from six European cohorts. We investigated their associations with fetal growth using a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering each exposure independently. We corrected for exposure measurement error and tested for exposure–exposure and sex–exposure interactions.

Results

The DSA model identified lead blood level, which was associated with a 97 g birth weight decrease for each doubling in lead concentration. No exposure passed the multiple testing-corrected significance threshold of ExWAS; without multiple testing correction, this model was in favour of negative associations of lead, fine particulate matter concentration and absorbance with birth weight, and of a positive sex-specific association of parabens with birth weight in boys. No two-way interaction between exposure variables was identified.

Conclusions

This first large-scale exposome study of fetal growth simultaneously considered >100 environmental exposures. Compared with single exposure studies, our approach allowed making all tests (usually reported in successive publications) explicit. Lead exposure is still a health concern in Europe and parabens health effects warrant further investigation.

中文翻译：

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妊娠暴露与胎儿生长之间的关联。

背景

几种环境污染物被证明可能影响胎儿的生长，通常来自单次暴露的家庭研究，这些研究容易出现发表偏倚和共同暴露的混淆。暴露范式提供了避免选择性报告发现和控制共同暴露造成的混淆的观点。我们旨在描述胎儿生长与妊娠化学物质和外部暴露体的关联。

方法

在人类早期暴露组项目中，使用生物标志物和环境模型对来自六个欧洲队列的 1287 对母子进行了评估，评估了 131 次产前暴露。我们使用同时​​考虑所有暴露的缺失-替代-添加 (DSA) 算法和独立考虑每个暴露的暴露组关联研究 (ExWAS) 研究了它们与胎儿生长的关联。我们校正了暴露测量误差并测试了暴露 - 暴露和性别 - 暴露相互作用。

结果

DSA 模型确定了铅的血液水平，铅浓度每增加一倍，出生体重就会减少 97 克。没有暴露通过 ExWAS 的多重测试校正显着性阈值；在没有多次测试校正的情况下，该模型支持铅、细颗粒物浓度和吸光度与出生体重的负相关，以及对羟基苯甲酸酯与男孩出生体重的性别特异性正相关。未发现暴露变量之间的双向交互作用。

结论

这是第一次对胎儿生长的大规模暴露研究，同时考虑了超过 100 次环境暴露。与单次暴露研究相比，我们的方法允许明确所有测试（通常在连续出版物中报告）。在欧洲，铅暴露仍然是一个健康问题，对羟基苯甲酸酯对健康的影响值得进一步调查。